Abstract 51P
Background
DSP107 is a fusion protein that combines elements of SIRPα and the 4-1BB ligand (4-1BBL). Its SIRPα component targets CD47 on tumor cells, effectively activating macrophages by neutralizing the "don't eat me” signal, while simultaneously anchoring trimeric 4-1BBL to the tumor, to co-stimulate 4-1BB on activated immune cells in the tumor microenvironment. This results in tumor-localized, conditional activation of innate and adaptive immune responses. Phase 1 data demonstrated an excellent safety profile with no red blood cells binding and no hematological, hepatic or other dose limiting toxicities (DLTs). Here we describe safety and efficacy data from phase 2 microsatellite stable (MSS) colorectal (CRC) expansion cohort treated with DSP107 plus atezolizumab.
Methods
Stage 3b/4 MSS-CRC patients who progressed following 2 lines of therapy including standard chemotherapy and/or targeted antibodies (n=27), were treated with weekly IV DSP107 infusions (10 mg/kg) and atezolizumab (1200 mg) Q3W during 3-week treatment cycles. The majority (67%) had liver metastases and BRAF/KRAS mutations. Study objectives were safety, tolerability and preliminary efficacy. Restaging imaging was performed every 2 months and evaluated by RECIST v1.1 criteria.
Results
DSP107 with atezolizumab was well tolerated with no DLTs. The most frequent TRAEs were infusion-related reactions (IRR; 44.4%), fatigue (18.5%), grade 1 anemia and eosinophilia (11.1% each). IRRs were managed during subsequent infusions by reducing the infusion rate and administering IV fluids. A median PFS of 20 weeks was observed in 21 evaluable patients. Disease control was demonstrated in 62% of evaluable patients (13/21) including two patients with deep (≥80% target lesion reduction) and durable (>15 months) confirmed objective responses and disappearance of pulmonary and hepatic metastases.
Conclusions
DSP107 demonstrated a distinct safety and efficacy profile. These phase 2 data suggest that the combination of DSP107 with PD(L)1 blockade has anti-tumor activity in MSS CRC including in patients with liver metastases and warrants further clinical investigation.
Clinical trial identification
NCT04440735.
Legal entity responsible for the study
KAHR Medical.
Funding
KAHR Medical.
Disclosure
R. Chantre, S. Amsili, R. Tabakman, Y. Shwartz, A. Foley-Comer: Financial Interests, Personal, Full or part-time Employment: KAHR Medical. All other authors have declared no conflicts of interest.